Automatic microscope slide

ABSTRACT

An automated microscope specimen slide examination system processes a plurality of microscope specimen slides one at a time for microscopic examination. A specimen slide storage magazine is indexed to position each specimen slide for access by a horizontal feed mechanism which transfers the specimen slide onto a microscope stage which has controllable X, Y and Z axis positioning to move the specimen slide into the optical viewing field of the microscope, focus the image and conduct systematic examination over the desired area of the specimen by X-Y axis incremental motion. At the end of the examination the specimen slide is returned to the magazine and the procedure is repeated for the next specimen slide. Previously examined specimen slides that have been returned to the storage magazine may be automatically returned to the microscope stage for reexamination.

This is a continuation of application Ser. No. 920,157 filed June 29,1978, now U.S. Pat. No. 4,248,498, which is a continuation ofapplication Ser. No. 746,617 filed Dec. 1, 1976 now abandoned.

BACKGROUND OF THE INVENTION

Microscopes are widely used for the examination of biological andmineral specimens and often, as in the medical field, it is desirable toregularly examine large quantities of specimens such as the blood ofhospitalized patients. In such cases, electronic systems may be used toautomatically examine and analyze the optical images of the microscope.Where electronics systems are used for rapid analysis of microscopespecimen images it becomes desirable to automatically regularly andrapidly feed the specimens to the microscope optics. After analysis aspecimen would be removed to make room for the next specimen and wouldbe collected for either further examination, reference, record keepingor disposal.

A microscope specimen stage is the platform of the microscope whichsupports and carries the object to be examined. If the object to beexamined is to be viewed with transmitted light then it is necessary forthe specimen stage or support to have a light transmissive opening inalignment with the microscope objective lens light path. The specimenstage has this opening for light transmission in or near its center. Inorder that as much area of the specimen slide as possible be viewedduring examination of the specimen without sliding it about the specimenstage this opening in the specimen stage is made as large as possibleand exposes the full width of the specimen slide. If the specimen slidewere pushed onto the specimen stage while the specimen stage waspositioned in the light path of the objective and condenser lenses thespecimen slide would drop into this opening.

Specimen slides for use with microscopes at present are generally madeof transparent glass. This glass is extremely brittle and chips,abrades, and fractures very easily. What might otherwise be considerednormal and safe procedures for handling and clamping most othermaterials are generally not satisfactory for glass microscope specimenslides. The scraping action and the abrasiveness of the glass edges willquickly deteriorate and make useless many of the metal and plasticsurfaces contacted by it if excessive rubbing pressure is applied.Because of these scraping, chipping, fracturing and abrasivecharacteristics the glass microscope specimen slide must be handledgently and carefully. Heavy clamping of the glass surfaces and applyingexcessive surface and side pressures on it should be avoided. Whenmoving the specimen slide about, excessive rubbing of the glass edgesagainst metal and plastic surfaces should be avoided.

No matter how it is avoided elsewhere, clamping and guiding of the glassspecimen slide cannot be avoided on the microscope specimen stage. Ifthe specimen slide is to be seated securely and aligned properly it mustbe guided into position accurately and then clamped, but this clampingmust be done as gently as possible.

SUMMARY OF THE INVENTION

The automated microscope specimen slide system of the present inventionautomatically takes microscope specimen slides one at a time from astorage magazine and places them onto the microscope specimen stage inan area adjacent to the objective and condenser lens system and then thespecimen stage moves horizontally and carries the specimen slide intothe optical light path of the microscope objective lens for viewing. Theviewing is generally done electronically without operator interventionexcept where the operator wishes to check or review a specific item.Once the specimen slide is in the optical light path of the microscopeobjective lens a signal generated by the microscope viewing electronicswill activate the specimen stage assembly Z axis focusing control motorand move the microscope stage in a vertical direction until the specimenis in focus. Other signals generated by the system electronics willactivate the X and Y axis positional control motors and accurately movethe specimen slide about the horizontal examination plane and place thespecimen in any position or series of positions required for examinationof the specimen. Focusing of the specimen during these positionalchanges is automatically corrected by the microscope viewing electronicscontrol signals if required.

The specimen slide is pushed onto the microscope specimen stage from themagazine in which slides are stored to a position in which the specimenslide selected from the magazine is adjacent to the objective andcondenser lens system and out of the optical light path. The specimenstage opening in this adjacent position is bridged by a structuralmember temporarily positioned such that the specimen slide can be pushedonto the specimen stage when supported by the temporary filler. Afterthe specimen slide is seated the loaded specimen stage then moves intothe light path of the objective and condenser lenses for viewing of thespecimen while the filler stays behind and remains out of the opticalfield of view.

In the embodiment shown the specimen slide is placed directly onto themicroscope stage which is positioned in the loading area and waiting forthe specimen slide to arrive and be deposited upon it. An alternativewould be for the specimen slide to be placed in the loading area whenthe microscope stage is not there but is elsewhere in an adjacentposition. Then the microscope stage would move from this adjacentposition to the specimen slide loading position and pick up and retainthe waiting specimen slide.

Once the examination of the specimen is completed the specimen slide isremoved in order to make room for the next one. The specimen slide isput back into the magazine but could be channeled elsewhere if desired.When the specimen slide has been placed back into the specimen slidemagazine or otherwise removed from the specimen slide feed path then themagazine will automatically index to bring the next specimen slide intoposition for dispensing or feeding. The cycle is then continued and thenext specimen slide is fed to the microscope specimen stage forobservation.

After the examination of a particular series of specimen slides has beencompleted any individual specimen slide that requires re-examination canby either operator signals or by predetermined control signals be fedautomatically back into the microscope viewing optics for furtherexamination.

The object of the invention is to provide an improved automaticmicroscope specimen slide examination system having the foregoingfeatures and advantages.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a partial perspective view of the overall specimen slidestoring, feeding, and X-Y-Z axis translation and positioning portions ofthe microscope stage system of the invention.

FIG. 2 is a top plan view of the apparatus shown in FIG. 1 includingparts not shown in FIG. 1.

FIG. 3 is a right elevation view corresponding to FIG. 2 partiallybroken away to show the Y and Z axis translation and positioning driveswith the extent of Y axis motion shown in phantom.

FIG. 4 is a view similar to FIG. 3 with other parts broken away to showthe extent of focusing or Z axis travel.

FIG. 5 is a rear elevation view partially in section taken approximatelyalong 5--5 of FIG. 2.

FIG. 6 is a partial perspective view showing details of the specimenslide stage.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring now to the drawings showing the preferred embodiment of theinvention, the apparatus is oriented such that the specimen slide isalways in an essentially horizontal plane except where slightlongitudinal tilting may be used during the specimen slide transfer.This constant essentially horizontal position of the specimen slidemakes optimum use of gravity for locating, restraining, and holding thespecimen slide in place. Heavy clamping is avoided and where clamping isrequired only light gentle pressures are applied. Also, excessivepressures in sliding the specimen slide into spring loaded clips orclamps is avoided since the rubbing action has a detrimental abrasiveeroding action on the glass edges and corners and on the surfaces of thematerials contacted. However, where spring loaded guides and clips areused light pressures and low incidence contact angles are used.

SPECIMEN SLIDE MAGAZINE INDEXING ASSEMBLY

The specimen slide magazine indexing assembly generally designated 11has a group of specimen slides 12 that are retained and grouped in aspaced apart relationship within a magazine 13. A control drive motor 14indexes the magazine 13 successively so that the specimen slides 12 maybe properly dispensed to the microscope specimen stage 35 in specificorder or sequence. After examination the specimen slides 12 are returnedto the magazine 13 in the embodiment shown.

After the transparent glass specimen slides 12 have been prepared withthe object to be examined they are placed in the magazine 13 as shown.The magazine 13 may be designed to hold an convenient number of specimenslides, for example 60. The magazine is used primarily as a temporarystorage station from which to dispense and then recover specimen slidesduring the examination process but may also be used for long termstorage.

Once loaded with prepared specimen slides 12 the magazine 13 is placedinto a magazine support bracket 15 which is mounted on vertical ballbearing slides 20 and is in threaded engagement with a lead screw 16which may be of the recirculating ball type driven by control motor 14.Magazine 13 is secured in place by suitable retaining means such asdetents, not shown. When the magazine 13 is in place in the magazineindexing assembly 11, the specimen slides 12 within the magazine are ina horizontal plane. The specimen slides 12 are supported loosely ingrooves 17 formed on the interior of the magazine 13, and, if desired,may be restrained in the magazine by lightly tensioned spring clips (notshown). These spring clips may contact either the face or the edges ofthe specimen slides (or both) when the specimen slides are in thegrooves 17. These grooves 17 are open at one end at the front of themagazine to permit discharge of the specimen slides 12 for transfer tothe microscope stage 35. An elongated vertical opening 18 is provided inthe rear of the magazine 13 to permit a push bar 19 to enter and contactthe back edge of the selected specimen slide 12 and slide it onto thespecimen stage 35 of the microscope. The front of the magazine 13 isopen to allow the specimen slide entry into and exit from the magazine,but a thin cover (not illustrated) may be placed on the front of themagazine after loading to act as a dust cover and to prevent accidentalspillage during handling. This thin cover is slipped off when themagazine is inserted into the magazine support bracket and may beslipped on again when the magazine is to be removed.

Magazine indexing is preferably electronically controlled and programmedto rapidly position each specimen slide for dispensing in successiveorder or any other sequence by the slide transfer mechanism.

Other specimen slide storage receptacles than the described magazine maybe used and other specimen slide indexing or positioning techniques suchas a gravity feed may be used for placing the specimen slides into thedispensing or feeding position. These alternative methods however willgenerally lack the flexibility of the described system which permitsdispensing of specimen slides in any sequence desired and which alsopermits review of any number of previously examined specimen slides andin any order desired.

SPECIMEN SLIDE TRANSFER MECHANISM ASSEMBLY

There are two specimen slide transfer mechanisms used, one to push thespecimen slide 12 from the specimen slide magazine 13 onto themicroscope stage specimen slide seat 21 and 21' and the other to pushthe specimen slide 12 back into the magazine 13 after it has beenexamined. An alternative transfer mechanism could provide a singlemechanism in a push to load and then pull to unload arrangement insteadof the present push to load and then push to unload arrangement.

After the specimen slide magazine 13 has indexed to a specimen slidedispensing position the push bar 19 enters through the rear opening 18of the magazine 13 to contact the back edge of the specimen slide 12 andslides the specimen slide 12 into the microscope stage slide seat 21 and21'. The push bar 19 which contacts the end of the specimen slide 12 hasa channel shape with the flanges 23 of the channel pointing down. Acutout 22 makes the end of push bar 19 contact the specimen slide 12 attwo points. The flanges 23 of the push bar channel section are longerthan and overlap the thickness of the specimen slide 12 that they pushagainst. This is to insure full contact between the push bar and the endof the specimen slide. Grooves 24 are provided in the microscopespecimen stage 35 to allow clearance of the push bar channel flanges 23.

The pushing motion for the specimen slide 12 is essentially rectilinearand may be either essentially constant in speed or it may have acontrolled acceleration upon starting the specimen slide transfer and acontrolled deceleration upon bringing the specimen slide to rest at theend of its travel. Controlling the acceleration and deceleration of thespecimen slide transfer is useful in minimizing the inertia effects ofsudden starts and stops during the faster specimen slide transfer rates.

The push bar 19 may be actuated by any suitable linear motion devicesuch as a scotch yoke or cam, rack and pinion gears or a screw and nutthat is coupled to a drive means. In the embodiment shown a partialscotch yoke 25 and partial revolution reversible drive motor 26 areused.

Insertion of the specimen slide 12 into seated and retained position onthe stage seats 21, 21' is best illustrated in FIG. 6 where a fixed edgeguide 46 and spring clamping edge guide means 48 are provided. The means48 is a bowed spring wire 18 slidably supported in transverse openingsin posts 49 which are mounted on the projections of stage 35. Upon entryof a specimen slide one edge thereof contacts spring wire 48 with a lowangle of incidence and the flexing of wire 48 urges the other edge ofthe specimen slide against fixed edge guide 46. The inserting motionproceeds until the slide engages end stop 27 which may be undercut as at50 to positively retain the specimen slide.

The specimen slide 12 is pushed up against the specimen stage slide endstop 27 with spring loaded means 28 provided in the scotch yoke drive 25to allow the push bar 19 to push the specimen slide 12 firmly into theend stop 27 without crushing it or excessively impacting it. After thepush bar 19 has completed its forward push of the specimen slide 12 (anddwell if a dwell is used), then a reverse drive by motor 26 reverses thedirection of the push bar linear motion actuator 25 to move the push bar19 back to its starting position.

To remove the specimen slide 12 from the microscope specimen stage 35 acorresponding push bar mechanism (operating left to right in FIG. 2)comprises push bar 19', partial scotch yoke 25' and motor 26' energizedas desired to return the specimen slide 12 to the magazine 13.

MICROSCOPE STAGE POSITIONER ASSEMBLY

The microscope stage positioner assembly comprises a specimen slidestage 35 mounted on a precision motorized X-Y axis positioner assembly34 for moving and positioning the specimen along a horizontal planealong with motorized up and down Z axis movement for specimen focusing.

The sliding member 36 of X-Y axis positioner assembly 34 is mounted forsliding motion in the Y direction relative to the combined Y axis baseand X axis sliding member 50 by means of roller bearing linear slides37. The combined Y axis base and X axis sliding member 50 in turn ismounted for motion in the X direction by means of roller bearing linearslides 38 mounted on a combined X axis base and Z axis moving member 39.The precision crossed roller bearing linear slides 37, 38 provide forprecision low friction linear motion when the Y and X axis slidingmembers 36 and 50 are driven respectively by precision ball bearingscrews 41, 42 which are rotated by stepping control motors 43, 44 forpower and position control. The entire X--Y axis positioner assembly issupported on a Z axis positioner assembly 40 which is driven in thevertical direction as hereinafter described.

The specimen stage 35 protrudes out from the Y axis slide positionersliding member 36 and has a wide opening 45 in its center shown occupiedby filler 52 in FIGS. 1 and 6. Upon Y axis motion to place the specimenslide 12 between condenser lens 9 and objective lens 10 the filler 52remains behind and the opening 45 exposes the maximum area of thespecimen slide transparent surface to illumination for opticalobservation.

The specimen stage 35 has an edge guide 46 and an end stop 27 whichassist to constrain and position the specimen slide 12 during loadingonto the specimen stage 35. The end stop 27 may have a slight invertedbevel to help retain and push the specimen slide 12 downward against thestage support surfaces.

During transfer to the specimen stage 35 the specimen slide 12 is guidedinto and clamped against the edge guide 46 and retained against end stop27 by an elongated bow-shaped spring 48 which is mounted by slidablyprojecting through horizontal bore holes in posts 49 projecting upwardfrom the protruding ends of specimen stage 35. As a specimen slide 12 isdriven by push bar 19 the leading corner and edge engage the bow spring48 at a low angle of incidence. Progression of the specimen slide 12toward its seated position flexes the bow spring 48 by deflecting itfrom the path of one edge of the specimen slide 12, the other edge ofwhich is referenced against the edge guide 46. The bow spring 48 thusapplies a small transverse force to the edge of the specimen slide 12contacted to maintain the specimen slide 12 positioned against edgeguide 46. At the end of the travel of push bar 19, the specimen slide 12is accurately positioned against end stop 27 and edge guide 46 andretained in that position by the slight pressure exerted by bow spring48 against the free edge of the specimen slide 12.

An extended portion 51 of the X axis positioner sliding member 50 has anupwardly extending surface 52 which serves as a bridge or filler for thespecimen stage center opening 45. This filler 52 is functional only whenthe Y axis positioner sliding member 36 is in its retracted positionwith the specimen stage 35 removed from the viewing area of themicroscope objective lens 10. After a specimen slide 12 is loaded intoposition on the projecting supports that form the specimen slide seats21 and 21' of specimen stage 35 the Y axis positioner sliding member 36is extended by Y axis drive motor 43 to move the specimen stage 35outward and into the microscope objective lens viewing field. The filler52 remains behind thereby uncovering the center opening 45 in thespecimen stage 35 and exposing maximum specimen slide area to theoptical viewing field. This filler 52 is the specimen slide loadingposition prevents the specimen slide 12 from falling through thespecimen stage opening 45 during the specimen slide loading andunloading operation.

After the specimen slide 12 is positioned between the condenser lens 9and objective lens 10, focusing is accomplished by raising and loweringthe X-Y axis positioner assembly base 39. The base 39 is constrained tovertical motion by four rod guides 60 which project through linearrecirculating ball bearings 61 which prevent any lateral motion butpermit up and down movement. A horizontally moving inclined plane wedge63 rides on roller bearing linear slides 64, 65 and is attached to anactuator screw 68 that is driven by a servo control motor 67. The wedge63 vertically positions the Z axis positioner moving member 39 which issupported thereon by an under surface inclined to slide on the surfaceof the wedge 63. A servo signal from the microscope optics electronicswill activate the servo control motor 67 to turn the screw 68 and drivethe wedge 63 horizontally in or out thereby raising or lowering theassembly comprising combined Z axis moving member and X axis base 39,combined X axis moving member and Y axis base 50, Y axis moving member36 and specimen stage 35 for focusing. The servo control motor 67 may begeared for any desired speed reduction.

The condenser lens 9 is attached to the base of the X axis positionerbase 39 by bracket 69. This base and thus the condenser lens 9 does notmove laterally in the X-Y horizontal plane but does move up and down inthe Z axis with the focusing adjustment.

An alternative to the horizontally moving screw driven wedge used forfocusing would be for the X-Y axis positioner assembly to be raised upand down for focusing directly by either a vertical lead screw or rackand pinion. The lead screw or rack and pinion might obtain anyadditional motion reduction required for fine or accurate focusing bybeing driven by a gear train.

As previously described, the microscopic examination of the specimenslide can take place either visually or automatically by well knowntechniques such as cell counting. For this purpose the X and Ypositioning systems can be controlled manually or automatically. Thusafter focusing by operating the Z-axis drive 67, the specimen slidecarried by the stage may be moved to any desired location relative tothe optical axis by actuation of the Y-axis drive 43 and the X-axisdrive 44. For automatic examination the drives 43, 44 would be energizedunder scan or other program control.

Upon completion of the examination of a slide the horizontal positioningY-axis drive returns the specimen slide on the stage to the positionover filler 52 to permit push rod 19' to drive the slide back to storageposition in the magazine, as previously described.

The operation of the disclosed embodiment will now be clear to thoseskilled in the art. While a particular embodiment has been disclosed,many modifications thereof which, without being limited thereto, includethose suggested herein, will be apparent and are to be considered aswithin the scope of the invention which is defined by the appendedclaims.

I claim:
 1. A bio-medical microscope specimen slide positioningapparatus adapted for use in automatic sequential examination of a groupof microscope specimen slides and comprising:a storage magazine forstoring a plurality of said microscope specimen slides; means for saidmagazine operable for indexing a specimen slide to a specimen slide exitor entry position; specimen slide transfer means positioned relative tosaid storage magazine for removing and transporting from said magazinesaid specimen slide located in said magazine and positioned at saidspecimen slide exit or entry position; a microscope specimen slide stagefor receiving a specimen slide from said magazine; means for positioningand retaining said specimen slide on said specimen slide stage;translation means for moving and positioning said stage with a specimenslide supported thereon in a geometric plane; and means for mounting tothe apparatus a microscope optical viewing system in a dispositionadjacent to said retained specimen slide such that by operation of saidtranslation means said specimen slide can be moved about and positionedin the optical axis of said optical viewing system for opticallyexamining the specimen on said specimen slide; said specimen slidetransfer means including means positioned relative to said stage forremoving said specimen slide from said stage after microscopeexamination.
 2. Apparatus according to claim 1 and further comprising asubstage condenser lens system operable for focusing on and directingconcentrated light through said stage retained specimen slide at thearea of said specimen slide being examined and into said microscopeoptical viewing system: and an objective lens assembly of saidmicroscope optical viewing system positioned to receive the concentratedlight directed through the stage retained specimen slide and into saidmicroscope optical viewing system by said substage condenser lenssystem.
 3. Apparatus according to claim 2 and further comprising meansfor focusing said microscope optical viewing system on the specimenslide when said specimen slide is retained by said stage.
 4. Apparatusaccording to claim 1, wherein said translation means serves to move saidstage in a horizontal plane and there is provided further positioningmeans supporting said translation means and operable for moving saidstage with a specimen slide supported therein vertically.
 5. Apparatusacording to claim 1, wherein said positioning means comprises an X-Yaxis table with an upper slide assembly and a lower slide assembly, eachsaid slide assembly being composed of an upper movable member and alower stationary member and said lower slide assembly supporting saidupper slide assembly at a right angle to said lower slide assembly forslidable motion along rectangular co-ordinates.
 6. Apparatus accordingto claim 1, wherein said specimen slide transfer means includes a barfor engaging the end of a specimen slide.
 7. Apparatus according toclaim 1, wherein said storage magazine is vertical and has horizontalgrooves for loosely retaining said specimen slides, an opening in oneend of said grooves for entry and exit of said specimen slides, a stopat the other end of said grooves to position and retain said specimenslides and an opening in said storage magazine for said specimen slidetransfer means to enter and engage and then project a specimen slide outof said storage magazine.
 8. Apparatus according to claim 1, whereinsaid specimen slide transfer means for projecting a specimen slide outof said storage magazine has controlled smooth motion acceleration anddeceleration means.
 9. Apparatus according to claim 1, wherein saidspecimen slide transfer means further includes end means for pushingsaid specimen slide on said specimen slide stage back into saidmagazine.
 10. Apparatus according to claim 1, wherein said storagemagazine, said microscope specimen slide stage and said microscopeoptical viewing system (when mounted to the apparatus) are positioneddirectly adjacent to each other so as in use of the apparatus to enabletransfer of the specimen slide projected form said magazine into theoptical axis of said optical viewing system in a minimal span ofdistance.
 11. Apparatus according to claim 1, and including a supportingstructure for use in transporting said specimen slide to the microscopespecimen slide stage loading position and adapted so that, in use of theapparatus, said supporting structure remains behind as the loadedspecimen slide stage moves the specimen slide, in use of the apparatus,into the optical axis of said microscope optical viewing system. 12.Apparatus according to claim 1 wherein said specimen slide transfermeans includes means for absorbing the over-travel motion so as not tobreak said specimen slide at the end of said specimen slide transfermovement of specimen slide stage.